Non-typhoidal Salmonella (NTS) is an important public health problem worldwide. Globally, NTS is estimated to be responsible for 93.8 million cases of gastroenteritis and 155,000 deaths annually [1] . NTS is one of the major foodborne illnesses in human of all age. NTS also infects groups of people with compromised immune systems. NTS infections cause morbidity and mortality both in developing and developed countries with highest annual incidence in parts of Africa (320 per 100,000), Asia (3200 per 100,000), Europe (690 per 100,000) and America (250 per 100,000) population [2] .

Consumption of animal-derived food products and direct and/or indirect contact with animals are the major routes of acquiring infection with NTS [3] [4] . NTS can also be transmitted from person to person or from contact with pets such as cats, dogs, rodents, reptiles, or amphibians [5] - [7] . NTS usually causes self-limiting gastroenteritis characterized by diarrhea, abdominal pain and vomiting in people of all ages [8] . However, in children, the elderly and immunocompromised patients, severe invasive disease with complicated extra-intestinal illness, bacteremia and meningitis can also be observed [9] .

Emergence of resistance to antibiotics in NTS is becoming a serious worldwide problem. Because of increased resistance to conventional antibiotics, fluoroquinolone (FQ) has become the drug of choice for the treatment of infections caused by multidrug-resistant NTS [10] [11] . However, increasing resistance to FQ among NTS isolates is also becoming a global concern that complicates antimicrobial therapy. Antimicrobial resistance to FQs is increasing chiefly due to the overuse of the drug for treatment of various infections and due to its misuse in animal feeds [9] [12] . Studies from across the globe have reported up to 54% of FQ resistance among NTS isolates [13] [14] . The major molecular mechanism contributing to FQ resistance among NTS strains is point mutations in hyper-variable quinolone-resistant determining regions (QRDR) of gyrA gene encoding DNA gyrase and parC gene encoding topoisomerase IV [15] - [17] .

The limited data available from Kingdom of Saudi Arabia (KSA) show variable occurrence of NTS infection in various regions of the country. Study from Makkah reports three-fold increase in cases of food poisoning in the last decade during Hajj season [18] . NTS food poisoning cases with 2% to 15% of FQ resistance have also been reported from Riyadh [18] , from Eastern province [19] and from Al-Hofuf [20] . NTS infections from Jeddah have been reported in 45% of meat samples from the butcher shops. However, no data are available about NTS infections in human from Jeddah. Since there is no/limited data available about NTS infections from KSA, therefore this study investigates the phenotypic antibiotic susceptibility among NTS isolates. Study also explored phenotypic and genotypic correlation for FQ resistance among NTS isolates.

NTS infections are an important public health problem worldwide, causing food poisoning and enteric infection to people of all ages [23] [24] . Since the occurrence of NTS infection and frequency of antimicrobial resistance among NTS isolates vary in different geographical location [25] - [27] , therefore, this study explored the frequency of NTS infection, phenotypic antibiotic susceptibility of important treatment regime including CIP and genotypic susceptibility profile of CIP for NTS isolates.

The demographic data of NTS patients from this study revealed that the occurrence of NTS infection is comparable in both male and female patients. Findings from this study also revealed that the NTS infection is more common among the middle age individuals as compared to old and very young people. Similar findings have also been reported previously in studies from Israel [28] and from United Kingdom [29] . This may also imply with the fact that middle age people tend to have more frequent outside eating for business and social outings as compared to the very young or old people which may be the source of higher NTS infections among them. Data from this study also showed that the Saudi national patients were largely affected with NTS infections as compared to expatriates. This may indicate that local Saudis are more susceptible to NTS as compared to non-Saudis which need further investigations. Most of non-Saudi infected patients were from Philippine this may also be compared with reports of higher occurrence of NTS infections in Philippine [30] .

Globally, rising resistance pattern of Ampicillin, trimethoprim/sulfamethoxazole and Ciprofloxacin among NTS has been reported which is posing a serious problem in the treatment of infections [31] [32] . The antibiogram from this study showed higher rate of resistance to SXT as compared to Amp and CIP, which is consistent with the finding of studies from several European countries [33] - [35] . However, studies from Denmark and Finland have reported higher resistance to CIP among NTS isolates [33] [34] . Besides, a number of epidemiological studies have also shown reduced susceptibility to CIP among NTS isolates [36] [37] . Thus, it was encouraging to see that less than fifty percent of NTS isolates in this study showed resistance to CIP which is an important antibiotic used across for the treatment of various types of infections.

Molecular characterization of gyrA and parC genes for CIP resistance among NTS isolates revealed mutation

^*Mutations were significantly associated with resistant (R) NTS isolates than susceptible (S) using Chi-square test (p-value = 0.023).

at only four codons; 83 and 87 of gyrA and 57 and 80 of parC, which is consistent with previous reports [38] [39] . The most commonly mutated codons were 83 and 87 of gyrA gene resulting in reduced susceptibility to CIP among NTS isolates. Similar finding has also been reported previously [40] . Even though none of the susceptible NTS isolates revealed mutations either in gyrA or parC genes, however, more than fifty percent of intermediately resistant NTS isolates exhibited single mutation at codon 83 of gyrA gene. Whereas, most of the NTS isolates exhibited double mutation either with 83 of gyrA or with codons 57 and 80 of parC gene to exhibit complete resistance to CIP as reported previously [41] [42] . This may indicate that variation at genetic level arises with single mutation before phenotypic resistance to CIP. Thus, molecular characterization of the genes may play an essential role in predicting future phenotypic resistance for CIP among the NTS isolates, which may assist in appropriate therapy and controlling the emergence of resistant NTS strains.

Based on the findings of this study, we conclude that NTS infection is prevalent in Jeddah among Saudi nationals. Findings of this study also suggest that cautious therapeutic use of FQ as prevalent mutations in intermediate susceptible NTS isolates may lead to resistant strains. Moreover, molecular characterization of FQ resistance genes could essentially be used for early detection of pre-FQ resistant NTS isolates, which may serve as an essential guide to clinicians for an appropriate therapy and containment of FQ resistant NTS infections. Data from this study also suggest that further studies to explore alternate FQ resistance mechanism(s) as no mutations are observed in respective FQ resistance genes among more than half of the FQ resistant NTS isolates. However, since this study is carried out in Jeddah, with limited sample size, therefore, further investigations with larger NTS sample are required to ascertain the findings of this study.

We would like to thank Majid A. Alharbi, Chair, Department of Pathology and Laboratory Medicine, for providing NTS isolates and demographic information of the patients for this study. We are greatly thankful to King Abdulaziz University, Jeddah, KSA, for providing the laboratory space and other facilities to carry out this research.

Ruaa A. Lahzah,Asho Ali, (2016) Association of Phenotypic and Genotypic Fluoroquinolone Susceptibility among Non-Typhoidal Salmonella Isolates from Jeddah, KSA. Journal of Biosciences and Medicines,04,100-109. doi: 10.4236/jbm.2016.44013

Abbreviations: s^* = Saudi, Ns' = Non-Saudi, M" = Male, F = Female, S′ = Susceptible, R″ = Resistance, I‴ = Intermediate.

S′ = Sensitive I″ = Intermediate R‴ = Resistance CIP^~ = Ciprofloxacin Seȓ = Serine Tyr̒ = Tyrosine Phe̓ = Phenylalanine Asp̔ = Aspartic acid Asn̚ = Asparagine Thr̾ = Theronine Trp͆ = Tryptophan Gly͛ = Glycine Iie͒ = Isoleucine.